Mammalian Notch is modified by d-Xyl-α1-3-d-Xyl-α1-3-d-Glc-β1-O-Ser: Implementation of a method to study O-glucosylation
Bibliographic record
Abstract
Notch is a key cell surface protein receptor that is a vital component of intercellular signaling occurring during development. The O-glucosylation of the extracellular Notch epidermal growth factor-like (EGF) repeats has recently been found to play an important role in the proper functioning of Notch in Drosophila. Previous efforts to identify the fine structure of the O-glucose-containing glycan of mammalian Notch have been hindered by limitations associated with approaches used to date. Here, we report the development of an alternative strategy that can be used to study this modification from a range of different tissues. To implement this approach, we have generated standards of the D-Xyl-alpha1-3-D-Xyl-alpha1-3-D-Glc trisaccharide, isomers of this structure, as well as the d-Xyl-alpha1-3-d-Glc disaccharide found previously on secreted EGF-containing proteins of the blood coagulation cascade. Following derivatization with 8-aminopyrene-1,3,6-trisulfonate (APTS), we use these standards in capillary electrophoretic analyses of O-glycans released from Notch1 EGF repeats in conjunction with exo-alpha-xylosidase digestion. These studies collectively reveal that the O-glucose-containing glycan decorating mammalian Notch is the D-Xyl-alpha1-3-D-Xyl-alpha1-3-D-Glc trisaccharide; an assignment in accord with previous predictions. Given the demonstrated importance of this modification in the function of Notch in Drosophila, we expect that the identification of this glycan decorating mammalian Notch1 should aid studies into the functional role of O-glycosylation of mammalian Notch isoforms. Wider application of this approach should facilitate identification of other EGF-containing proteins bearing this O-glycan and aid in their study.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".